tbuckley/cabot-search huggingface dataset:
411 Long term laboratory safety of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis
Authors: Elaine Siegfried, Michael J Cork, Benjamin  Lockshin, Mark Boguniewicz, Sumeet  Uppal, Faisal A Khokhar, Ashish Bansal, Debra Sierka, Sonya Cyr
Journal: British Journal of Dermatology (2023)

Abstract Systemic treatments often require laboratory monitoring. Here we report 52-week laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe AD. LIBERTY AD PED-OLE (NCT02612454) is an open-label extension study of children aged 6 months to &amp;lt;18 years with moderate-to-severe AD. This analysis includes hematologic and chemistry laboratory parameters in children aged 6 months to 5 years treated with dupilumab every 4 weeks (q4w; 200 mg: ≥5 to &amp;lt;15 kg; 300 mg: ≥15 to &amp;lt;30 kg). Of the 180 patients enrolled, 122 (67.8%) completed up to 16 weeks and 30 (16.7%) completed up to 52 weeks. Mean (SD) eosinophil counts increased slightly from baseline [1.15 × 109/L (1.18) ] to Week 16 [1.5 × 109/L (1.91)], but then decreased below baseline by Week 52 [0.80 × 109/L (0.64)]. Mean (SD) platelet counts were relatively stable with a modest decrease from baseline [388.7 × 109/L (102.51)] to Week 52 [356.1 × 109/L (107.48)]. Chemistry parameters remained within the normal reference ranges. One patient (0.6%) reported a mild case of anemia, and one patient (0.6%) reported a mild case of thrombocytopenia, which were resolving and resolved at the time of this interim analysis, respectively. Overall safety was consistent with the known dupilumab safety profile. No clinically meaningful changes in hematologic and chemistry parameters were observed during 52 weeks of dupilumab treatment. As with adults, adolescents and older children, routine laboratory monitoring is unnecessary in children aged 6 months to 5 years with moderate-to-severe AD.
Diagnosis of vocal cord dysfunction/inducible laryngeal obstruction: An International Delphi Consensus Study
Authors: Paul Leong, Anne E. Vertigan, Mark Hew, Malcolm Baxter, Debra Phyland, James H. Hull, Thomas L. Carroll, Peter G. Gibson, Vanessa M. McDonald, Thomas Halvorsen, Hege Havstad Clemm, Maria Vollsæter, Ola Drange Røksund, Philip G. Bardin
Journal: Journal of Allergy and Clinical Immunology (2023)
UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders
Authors: Xinliang Lu, Xianghui Kong, Hao Wu, Jiayue Hao, Sirui Li, Zichun Gu, Xianchang Zeng, Yingying Shen, Shibo Wang, Jiming Chen, Xuefeng Fei, Yi Sun, Xu Li, Lingling Jiang, Fei Yang, Jianli Wang, Zhijian Cai
Journal: Cell Metabolism (2023)
Electronic nose in differentiating and ascertaining clinical status among patients with pulmonary nontuberculous mycobacteria: A prospective multicenter study
Authors: Meng-Rui Lee, Hung-Ling Huang, Wei-Chang Huang, Shang-Yu Wu, Pang-Chun Liu, Jui-Ching Wu, Meng-Hsuan Cheng, Chau-Chyun Sheu, Kea-Tiong Tang, Jann-Yuan Wang, Chao-Chi Ho, Jin-Yuan Shih, Inn-Wen Chong
Journal: Journal of Infection (2023)
Treatment of Pneumococcal Pneumonia
Authors: R Pallares
Journal: New England Journal of Medicine (1941)

The emergence of Streptococcus pneumoniae strains with resistance to penicillin, macrolide, and other drugs has made the treatment of pneumococcal infections more complicated. Although resistance to penicillin has had a profound impact on the outcome of meningitis, it has had little impact on the mortality from pneumococcal pneumonia because the serum and pulmonary levels achieved with penicillin (or related drugs) are several times higher than the minimal inhibitory concentration of the strains. Thus, based on current levels of resistance to penicillin and cephalosporin, most patients with mild/moderate pneumococcal pneumonia may respond to oral amoxicillin, and most with severe pneumonia may be successfully treated with intravenous ceftriaxone, cefotaxime, or amoxicillin-clavulanic acid. It is of concern that patients infected with erythromycin-resistant pneumococci may not respond to therapy with a macrolide. In our opinion, except for well-selected patients, imipenem and vancomycin should not be widely used for the treatment of pneumococcal pneumonia. Some new drugs such as the new quinolones may play an important role in the management of pneumonia in the near future.
Cover Image, Volume 43, Issue 5
Authors: Stephen Keelan, Mihaela Ola, Sara Charmsaz, Sinéad Cocchiglia, Daniela Ottaviani, Seán Hickey, Siobhan Purcell, Fiona Bane, Aisling Hegarty, Ben Doherty, Katherine Sheehan, Lance Hudson, Nicola Cosgrove, Benjamin Roux, Muriel Laine, Geoffrey Greene, Damir Varešlija, Arnold Konrad Hill, Leonie Young
Journal: Cancer Communications (2023)

The cover image is based on the Correspondence Dynamic epi-transcriptomic landscape mapping with disease progression in estrogen receptor-positive breast cancer by Stephen Keelan et al., https://doi.org/10.1002/cac2.12407.
The neuroprotective effect of traditional Chinese medicinal plants—A critical review
Authors: João Moreira, Mariana Machado, Mónica Dias-Teixeira, Ricardo Ferraz, Cristina Delerue-Matos, Clara Grosso
Journal: Acta Pharmaceutica Sinica B (2023)

Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.
Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study
Authors: Abi Manesh, Emily Devasagayam, Kundakarla Bhanuprasad, Lalee Varghese, Regi Kurien, Lisa M. Cherian, Divya Dayanand, Mithun M. George, Selwyn S. Kumar, Rajiv Karthik, Harshad Vanjare, Jayanthi Peter, Joy S. Michael, Meera Thomas, Binu S. Mathew, Prasanna Samuel, Pimnara Peerawaranun, Mavuto Mukaka, Vedantam Rupa, George M. Varghese
Journal: Clinical Microbiology and Infection (2023)

To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis.This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome.Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes.Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.
Attenuation of amyloid‐β‐induced mitochondrial dysfunction by active components of anthocyanins in HT22 neuronal cells
Authors: Jing Li, Pan Wang, Ming‐Jie Hou, Bao Ting Zhu
Journal: MedComm (2023)

Alzheimer's disease (AD) is a common form of neurodegenerative disease in the elderly. Amyloid-
Monocyte-derived macrophages orchestrate multiple cell-type interactions to repair necrotic liver lesions in disease models
Authors: Dechun Feng, Xiaogang Xiang, Yukun Guan, Adrien Guillot, Hongkun Lu, Chingwen Chang, Yong He, Hua Wang, Hongna Pan, Cynthia Ju, Sean P. Colgan, Frank Tacke, Xin Wei Wang, George Kunos, Bin Gao
Journal: Journal of Clinical Investigation (2023)

The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor 9+ (SOX9+) hepatocytes near the necrotic lesions, which acted as a barrier from further injury. Subsequently, necrotic environment (hypoxia and dead cells) induced a cluster of complement 1q-positive (C1q+) MoMFs that promoted necrotic removal and liver repair, while Pdgfb+ MoMFs activated hepatic stellate cells (HSCs) to express α-smooth muscle actin and induce a strong contraction signal (YAP, pMLC) to squeeze and finally eliminate the necrotic lesions. In conclusion, MoMFs play a key role in repairing the necrotic lesions, not only by removing necrotic tissues, but also by inducing cell death-resistant hepatocytes to form a perinecrotic capsule and by activating α-smooth muscle actin-expressing HSCs to facilitate necrotic lesion resolution.
Inhibition of a new AXL isoform, AXL3, induces apoptosis of mantle cell lymphoma cells
Authors: Pascal Gelebart, May Eriksen Gjerstad, Susanne Benjaminsen, Jianhua Han, Ida Karlsen, Mireia Mayoral Safont, Calum Leitch, Zinayida Fandalyuk, Mihaela Popa, Lars Helgeland, Bela Papp, Fanny Baran-Marszak, Emmet McCormack
Journal: Blood (2023)

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells. Interestingly, functional characterization of AXL3, using CRISPR inhibition, revealed that only the knock down of this isoform leads to apoptosis of MCL cells. Importantly, pharmacological inhibition of AXL activity resulted in a significant decrease in the activation of well-known proproliferative and survival pathways activated in MCL cells (ie, β-catenin, Ak strain transforming, and NF-κB). Therapeutically, preclinical studies using a xenograft mouse model of MCL indicated that bemcentinib is more effective than ibrutinib in reducing the tumor burden and to increase the overall survival. Our study highlights the importance of a previously unidentified AXL splice variant in cancer and the potential of bemcentinib as a targeted therapy for MCL.
Table of Contents
Authors: Gerhard Malnic, Adriana Girardi, Rolf Stahl, Elion Hoxha, William Couser, Tobias Huber, Caroline Stigant, Katherine Barraclough, Mark Harber, Nigel Kanagasundaram, Charu Malik, Vivekanand Jha, Raymond Open, Reiko Inagi, Kentaro Yoshioka, Mark Hanudel, Mark Koury, Volker Haase, Chunni Lu, A Kitching, Roger Evans, Paola Romagnani, Laura Barisoni, Masaomi Nangaku, Peter Boor, Alessia Fornoni, Jürgen Floege, P Coates, Jonathan Himmelfarb, Rachel Lennon, Hans-Joachim Anders, Benjamin Humphreys, Fergus Caskey, Agnes Fogo, Mohamed Hmida, Tahar Mechichi, Giorgina Piccoli, Mohamed Ksibi, Steffen Grampp, René Krüger, Victoria Lauer, Sebastian Uebel, Karl Knaup, Julia Naas, Verena Höffken, Thomas Weide, Mario Schiffer, Stephanie Naas, Johannes Schödel, Violante Olivari, Simona Di Modica, Maria Lidonnici, Mariam Aghajan, Celia Cordero-Sanchez, Emanuele Tanzi, Mariateresa Pettinato, Alessia Pagani, Francesca Tiboni, Laura Silvestri, Shuling Guo, Giuliana Ferrari, Antonella Nai, Georg Herrnstadt, Christoph Niehus, Torben Ramcke, Julia Hagenstein, Laura-Isabell Ehnold, Anna Nosko, Matthias Warkotsch, Frederic Feindt, Simon Melderis, Hans-Joachim Paust, Varshi Sivayoganathan, Saskia-Larissa Jauch-Speer, Milagros Wong, Daniela Indenbirken, Christian Krebs, Ulf Panzer, Victor Puelles, Malte Kluger, Oliver Steinmetz, Tobias Sieckmann, Gunnar Schley, Neslihan Ögel, Simon Kelterborn, Felix Boivin, Michael Fähling, Muhammad Ashraf, Martin Reichel, Emilia Vigolo, Andrea Hartner, Falk-Bach Lichtenberger, Tilman Breiderhoff, Felix Knauf, Christian Rosenberger, Felix Aigner, Kai Schmidt-Ott, Holger Scholz, Karin Kirschner, Wen-Bin Liu, Guang-Rui Huang, Bao-Li Liu, Hai-Kun Hu, Jie Geng, Hong-Liang Rui, Chang Gao, Yu-Jiao Huang, Gui-Yang Huo, Jia-Rong Mao, Chuan-Jian Lu, An-Long Xu
Journal: Kidney International (2023)
Integrative multi-omics deciphers the spatial characteristics of host-gut microbiota interactions in Crohn’s disease
Authors: Xiang Gao, Ruicong Sun, Na Jiao, Xiao Liang, Gengfeng Li, Han Gao, Xiaohan Wu, Muqing Yang, Chunqiu Chen, Xiaomin Sun, Liang Chen, Wei Wu, Yingzi Cong, Ruixin Zhu, Tiannan Guo, Zhanju Liu
Journal: Cell Reports Medicine (2023)

(Cell Reports Medicine 4, 101050; June 20, 2023) In the originally published version of this article, Dr. Xiao Liang was incorrectly presented without an equal contribution footnote. This has since been corrected online. The authors regret this error. Integrative multi-omics deciphers the spatial characteristics of host-gut microbiota interactions in Crohn's diseaseGao et al.Cell Reports MedicineMay 11, 2023In BriefGao et al. delineate the spatial characteristics of host proteins and gut microbiota and their interactions via integrative multi-omics analysis of the intestine and its accessory tissues from patients with Crohn's disease. This study provides an in-depth understanding of the pathogenesis and diagnostic potential of signature proteins and microbes. Full-Text PDF Open Access
Correction: Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells
Authors: Tze-Sian Chan, Chung-Chi Hsu, Vincent C. Pai, Wen-Ying Liao, Shenq-Shyang Huang, Kok-Tong Tan, Chia-Jui Yen, Shu-Ching Hsu, Wei-Yu Chen, Yan-Shen Shan, Chi-Rong Li, Michael T. Lee, Kuan-Ying Jiang, Jui-Mei Chu, Gi-Shih Lien, Valerie M. Weaver, Kelvin K. Tsai
Journal: The Journal of Experimental Medicine (2023)

The bioluminescence images on days 11 and 21 of the "LDM" group in Fig. 8 A, which are provided as examples of tumor size on those days, are similar.The authors are certain that the two images are not the same; however, since the respective large-sized raw image files are no longer available, the authors cannot be certain that the images were collected at the time points listed.The two images have been removed from the corrected Fig. 8 A, shown here.The images in Fig. 8 A are representative only and do not impact the quantification and reproducibility of the data or the conclusions.The authors apologize for any confusion caused.
Green nephrology: a series of mini reviews on minimizing the environmental impact of kidney health care
Authors: Brendan Smyth, Maria Pippias, Shaifali Sandal, Winston Wing-Shing Fung, Isabelle Ethier, Dearbhla Kelly, Ehab Hafiz, Peace Bagasha, Ugochi Chika Onu, Workagegnehu Hailu Bilchut, Divya Bajpai, Vivekanand Jha, Letizia De Chiara
Journal: Kidney International (2023)
Putting data to work for precision medicine
Authors: Andreas Bjerrum, Ulrik Lassen
Journal: Cell Reports Medicine (2023)

We discuss the One Stop Shop for Clinical Research (OSCAR) project that links clinical data, patient-reported outcomes, genomic data, and health registry data, employing a rigorous data privacy protection technology, to provide insights into treatment efficacy and safety and serve as a comparator for single-arm trials. This could inspire further initiatives to advance precision medicine.
Sanggenon C inhibits cell proliferation and induces apoptosis by regulating the MIB1/DAPK1 axis in glioblastoma
Authors: Hongbo Chang, Jianbing Hou, Yaqian Shao, Minghao Xu, Xuelian Weng, Yi Du, Junbo Shi, Li Zhang, Hongjuan Cui
Journal: MedComm (2023)

Sanggenon C (SC), a herbal flavonoid extracted from Cortex Mori, has been mentioned to possess more than one treasured organic properties. However, the molecular mechanism of its anti-tumor impact in glioblastoma (GBM) remains unclear. In this study, we reported that SC displayed a GBM-suppressing impact in vitro and in vivo with no apparent organ toxicity. SC dramatically suppressed cell proliferation-induced cell apoptosis in GBM cells. Mechanistically, we unveiled that SC modulated the protein expression of death associated protain kinase 1 (DAPK1) by controlling the ubiquitination and degradation of DAPK1. Quantitative proteomic and Western blot analyses showed that SC improved DAPK1 protein degradation via decreasing the expression of E3 ubiquitin ligase Mindbomb 1 (MIB1). More importantly, the effects of SC on cell proliferation and apoptosis of GBM cells have been in part reversed through DAPK1 downregulation or MIB1 overexpression, respectively. These results indicated that SC might suppress cell proliferation and induce cell apoptosis by decreasing MIB1-mediated DAPK1 degradation. Furthermore, we found that SC acted synergistically with temozolomide (TMZ), an anti-cancer drug used in GBM, resulting in elevated chemotherapeutic sensitivity of GBM to TMZ. Collectively, our data suggest that SC might be a promising anti-cancer agent for GBM therapy.
Contents
Authors: Young Do, Mina Kim, Yoonjong Bae, Hyemin Jang, Dong Lim, Jason Betz, Hannah Behrens, Brooke Harkness, Richard Stutzman, Winston Chamberlain, Marie Blanco, Deborah Hegarty, Sue Aicher, Brooke Sherry, Samuel Lee, Maria De Los, Angeles Ramos Cadena, Gregory Laynor, Sheel Patel, Maxine Dellabadia Simon, Eric Romanowski, Sarah Hochman, Joel Schuman, Christina Prescott, Cassandra Thiel, Ron Hays, Scott Macrae, Jack Holladay, Michelle Tarver, Flora Lum, Walter Stark, Beverly Weidmer, Nisha Kumar, George Lau, Tieuvi Nguyen, Steven Schallhorn, Malvina Eydelman, Samuel Masket
Journal: Ophthalmology (2023)
A benchmark of computational pipelines for single-cell histone modification data
Authors: Félix Raimundo, Pacôme Prompsy, Jean-Philippe Vert, Céline Vallot
Journal: Genome biology (2023)

Single-cell histone post translational modification (scHPTM) assays such as scCUT&Tag or scChIP-seq allow single-cell mapping of diverse epigenomic landscapes within complex tissues and are likely to unlock our understanding of various mechanisms involved in development or diseases. Running scHTPM experiments and analyzing the data produced remains challenging since few consensus guidelines currently exist regarding good practices for experimental design and data analysis pipelines.We perform a computational benchmark to assess the impact of experimental parameters and data analysis pipelines on the ability of the cell representation to recapitulate known biological similarities. We run more than ten thousand experiments to systematically study the impact of coverage and number of cells, of the count matrix construction method, of feature selection and normalization, and of the dimension reduction algorithm used. This allows us to identify key experimental parameters and computational choices to obtain a good representation of single-cell HPTM data. We show in particular that the count matrix construction step has a strong influence on the quality of the representation and that using fixed-size bin counts outperforms annotation-based binning. Dimension reduction methods based on latent semantic indexing outperform others, and feature selection is detrimental, while keeping only high-quality cells has little influence on the final representation as long as enough cells are analyzed.This benchmark provides a comprehensive study on how experimental parameters and computational choices affect the representation of single-cell HPTM data. We propose a series of recommendations regarding matrix construction, feature and cell selection, and dimensionality reduction algorithms.
Tackling Structural Injustices: On the Entanglement of Visibility and Justice in Emerging Technologies
Authors: Matthias Braun, Hannah Bleher, Eva Maria Hille, Jenny Krutzinna
Journal: The American Journal of Bioethics (2023)

This article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical CareBounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine
An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma
Authors: Qiujun Qiu, Sunhui Chen, Huining He, Jixiang Chen, Xinyi Ding, Dongdong Wang, Jiangang Yang, Pengcheng Guo, Yang Li, Jisu Kim, Jianyong Sheng, Chao Gao, Bo Yin, Shihao Zheng, Jianxin Wang
Journal: Acta Pharmaceutica Sinica B (2023)

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.